Additional Study Information: The purpose of this research study is to evaluate the safety and effectiveness (how well the study drug works) of NBTRX3 administered via intratumoral injections (injected directly into tumor) and used together with radiotherapy or radiotherapy combined with cetuximab, and how it compares with radiotherapy alone, or radiotherapy combined with cetuximab. NBTXR3 holds nanoparticles called hafnium oxide that works to increase the energy dose deposit within tumor cells when they are activated by ionizing radiation, which destroys cancer cells by causing damage to their membranes. NBTXR3 is an investigational new drug, which means that NBTXR3 has not been approved by the U.S. Food and Drug Administration (FDA). Cetuximab has been approved by the U.S. Food and Drug Administration (FDA) and is being used according to its label. This study has two study arms. Arm A will receive one dose of the study drug one time, followed by the usual radiotherapy, either with or without targeted therapy (cetuximab), used for this type of cancer. Arm B will get the usual radiotherapy, either with or without targeted therapy (cetuximab), used for this type of cancer. Targeted therapy is a type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread. This is a randomized study, which means that a computer will by chance assign you to one of the arms in this study. This is done by chance because no one knows if one study group is better or worse than the others. Your study doctor will not have any influence as to which study group you will be assigned.